A5066069860- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Cancer therapeutics and mechanisms
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- Biochemical and Molecular Research
- Aging and Gerontology Research
- Health disparities and outcomes
- Microbial Natural Products and Biosynthesis
- Single-cell and spatial transcriptomics
- COVID-19 and Mental Health
- Retinal Development and Disorders
University of Colorado Anschutz Medical Campus
2021
Northwestern University
2020
Université Paris-Sud
2020
Broad Institute
2018-2019
ABSTRACT During retinal development, a large subset of progenitors upregulates the transcription factor Otx2, which is required for photoreceptor and bipolar cell formation. How these progenitor cells initially activate Otx2 expression unclear. To address this, we investigated cis-regulatory network that controls in mice. We identified minimal enhancer element, DHS-4D, drove newly formed OTX2+ cells. CRISPR/Cas9-mediated deletion DHS-4D reduced OTX2 expression, but this effect was diminished...
The efficacies of all antibiotics against tuberculosis are eventually eroded by resistance. New strategies to discover drugs or drug combinations with higher barriers resistance needed. Previously, we reported the application a large-scale chemical-genetic interaction screening strategy called PROSPECT discovery new Mycobacterium inhibitors, which resulted in identification small molecule BRD-8000, an inhibitor novel target, EfpA. Leveraging chemical genetic profile identified BRD-9327,...
New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains Prioritize Expanded Chemistry Targets) in which we screen compounds against pools strains depleted for essential bacterial targets. engineered targeting 474 Mtb genes screened 100-150 activity-enriched unbiased libraries,...